The purpose of these studies is to determine the basic changes in the mechanisms controlling urinary bladder function which occur with aging. Particular attention will be paid to those mechanisms which alter the responses of the urinary bladder to drugs. Various aspects of urinary bladder function and properties of urinary bladder smooth muscle will be compared in young (4 month), mature (12 month) and old (24 month) rats. Both in vivo and in vitro experiments will be performed in each group. Cystometrograms will be performed under anesthesia to determine bladder capacity, micturition threshold and miximum bladder pressure during micturition. Pressure volume curves will also be performed immediately postmortem in order to separate the effects of urinary bladder innervation from the basic characteristics of bladder smooth muscle. Responses of urinary bladder in situ to stimulation of sympathetic and parasympathetic nerves will also be evaluated. Histological specimens of bladders from each age group will be evaluated for muscle thickness and presence of collagenous tissue. In isolated preparations of detrusor and trigonal muscle, the length-tension relationships of these muscles will be compared in younger and senescent animals and the response of these preparations to stimulatory drugs and nerve stimulation will be compared. Furthermore, the ability of drugs to alter the smooth muscle responses to nerve stimulation will be evaluated. These studies will use physiological and pharmacological techniques to determine the peripheral mechanisms which are altered during the aging process. A goal of these studies will be to develop an animal model of the aging human urinary bladder and to use this model to predict the effects of drugs in elderly humans. Ultimately, the model will be used to better understand the basic mechanisms which predispose many elderly humans to urinary incontinence and describe the mechanisms whereby certain drugs precipitate urinary incontinence. Furthermore, the model will be helpful for the development and prediction of drug therapy which might be used to ameliorate urinary incontinence.